Lipid profiles in middle-aged men and women after famine exposure during gestation: The Dutch Hunger Winter Families Study

Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY 10032, USA.
American Journal of Clinical Nutrition (Impact Factor: 6.77). 05/2009; 89(6):1737-43. DOI: 10.3945/ajcn.2008.27038
Source: PubMed

ABSTRACT Many studies in humans have related birth weight to lipid profiles in adulthood. Fewer have estimated associations directly attributable to maternal nutrition during pregnancy.
Our objective was to determine whether famine exposure during gestation is associated with a more atherogenic profile in adult offspring.
In 2003-2005, we studied 1) 359 singleton men and women born between January 1945 and March 1946 in clinics in Amsterdam, Rotterdam, and Leiden whose mothers were exposed to the famine during pregnancy; 2) 299 singletons born in the same 3 institutions during 1943 or 1947; and 3) 313 unexposed same-sex siblings of the above individuals. A lipid profile was obtained after an overnight fast.
Female offspring with prenatal famine exposure had a dyslipidemic pattern characterized by elevated total cholesterol (0.26 mmol/L; 95% CI: 0.07, 0.46; P = 0.007), triglycerides (0.17 mmol/L; 95% CI: 0.03, 0.31; P = 0.02), and LDL cholesterol (0.17 mmol/L; 95% CI: -0.01, 0.36; P = 0.06) compared with unexposed offspring. This pattern was not seen in men. The increases in total cholesterol and LDL cholesterol were independent of body mass index, waist circumference, and midthigh circumference. The increase in triglycerides was independent of midthigh circumference but was attenuated with control for either body mass index or waist circumference. There was no evidence for associations within specific gestational windows. No association was observed between prenatal famine exposure and HDL cholesterol in either sex.
In women, but not in men, aged approximately 58 y, we observed an association between prenatal undernutrition and elevated total cholesterol concentrations and triglycerides.

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Available from: Aryeh Stein, Jan 14, 2014
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    • "Even after more than a decade of research, no genetic or epigenetic variations have been identified that could explain the inheritance of this phenotype. Similarly, results from the Dutch Hunger Winter Families cohort [70] showed that a hunger period during pregnancy can lead to poor health of female offspring in the F1 and F2 generations [71], [72]. This inheritance pattern has been associated with DNA methylation changes in the human IGF2 gene, and several other studies have provided evidence suggesting that altered DNA methylation patterns may link nutritional exposures in the parental or grandparental generation to human health and life span [73]. "
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    ABSTRACT: Genomic concepts are based on the assumption that phenotypes arise from the expression of genetic variants. However, the presence of non-Mendelian inheritance patterns provides a direct challenge to this view and suggests an important role for alternative mechanisms of gene regulation and inheritance. Over the past few years, a highly complex and diverse network of noncoding RNAs has been discovered. Research in animal models has shown that RNAs can be inherited and that RNA methyltransferases can be important for the transmission and expression of modified phenotypes in the next generation. We discuss possible mechanisms of RNA-mediated inheritance and the role of these mechanisms for human health and disease.
    PLoS Genetics 04/2014; 10(4):e1004296. DOI:10.1371/journal.pgen.1004296 · 7.53 Impact Factor
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    • "Lipid profiles of adults exposed prenatally to famine exhibited sex bias independent of gestational timing: adult women who experienced prenatal nutrient restriction showed elevated total and LDL cholesterol and triglyceride concentrations, risk factors for cardiovascular disease, compared to unexposed women; men did not show such an increase [106]. Furthermore, Tobi et al. [107] compared DNA methylation patterns in 15 genes associated with metabolic and cardiovascular disease in individuals prenatally exposed to famine. "
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    ABSTRACT: Several autoimmune and neurological diseases exhibit a sex bias, but discerning the causes and mechanisms of these biases has been challenging. Sex differences begin to manifest themselves in early embryonic development, and gonadal differentiation further bifurcates the male and female phenotypes. Even at this early stage, however, there is evidence that males and females respond to environmental stimuli differently, and the divergent phenotypic responses may have consequences later in life. The effect of prenatal nutrient restriction illustrates this point, as adult women exposed to prenatal restrictions exhibited increased risk factors of cardiovascular disease, while men exposed to the same condition did not. Recent research has examined the roles of sex-specific genes, hormones, chromosomes, and the interactions among them in mediating sex-biased phenotypes. Such research has identified testosterone, for example, as a possible protective agent against autoimmune disorders and an XX chromosome complement as a susceptibility factor in murine models of lupus and multiple sclerosis. Sex-biased chromatin is an additional and likely important component. Research suggesting a role for X and Y chromosome heterochromatin in regulating epigenetic states of autosomes has highlighted unorthodox mechanisms of gene regulation. The crosstalk between the Y chromosomes and autosomes may be further mediated by the mitochondria. The organelles have solely maternal transmission and exert differential effects on males and females. Altogether, research supports the notion that the interaction between sex-biased elements might exert novel regulatory functions in the genome and contribute to sex-specific susceptibilities to autoimmune and neurological diseases.
    Biology of Sex Differences 01/2014; 5(1):2. DOI:10.1186/2042-6410-5-2 · 4.84 Impact Factor
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    • "The start of gestation was defined by the date of last menstrual period (LMP) as noted in the hospital records unless it was missing or implausible (12%). In case the LMP was missing, we derived the date from relevant annotations on the birth record and estimated gestational age from birthweight and date of birth, using cutoffs from tables of sex-, parity-and birthweight-specific gestational ages from the combined birth records of the Amsterdam midwifery school (1948 –1957) and the University of Amsterdam Obstetrics Department (1931– 1965) (Lumey et al., 2009). Subsequently, the most consistent and plausible estimation of gestational age was selected for each infant and used together with date of birth to derive the date of LMP. "
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    ABSTRACT: Is there an association between acute prenatal famine exposure or birthweight and subsequent reproductive performance and age at menopause? No association was found between intrauterine famine exposure and reproductive performance, but survival analysis showed that women exposed in utero were 24% more likely to experience menopause at any age. Associations between prenatal famine and subsequent reproductive performance have been examined previously with inconsistent results. Evidence for the effects of famine exposure on age at natural menopause is limited to one study of post-natal exposure. This cohort study included men and women born around the time of the Dutch famine of 1944-1945. The study participants (n = 1070) underwent standardized interviews on reproductive parameters at a mean age of 59 years. The participants were grouped as men and women with prenatal famine exposure (n = 407), their same-sex siblings (family controls, n = 319) or other men and women born before or after the famine period (time controls, n = 344). Associations of famine exposure with reproductive performance and menopause were analysed using logistic regression and survival analysis with competing risk, after controlling for family clustering. Gestational famine exposure was not associated with nulliparity, age at birth of first child, difficulties conceiving or pregnancy outcome (all P> 0.05) in men or women. At any given age, women were more likely to experience menopause after gestational exposure to famine (hazard ratio 1.24; 95% CI 1.03, 1.51). The association was not attenuated with an additional control for a woman's birthweight. In this study, there was no association between birthweight and age at menopause after adjustment for gestational famine exposure. Age at menopause was self-reported and assessed retrospectively. The study power to examine associations with specific gestational periods of famine exposure and reproductive function was limited. Our findings support previous results that prenatal famine exposure is not related to reproductive performance in adult life. However, natural menopause occurs earlier after prenatal famine exposure, suggesting that early life events can affect organ function even at the ovarian level. This study was funded by the NHLBI/NIH (R01 HL-067914). Not applicable.
    Human Reproduction 08/2013; 28(12). DOI:10.1093/humrep/det331 · 4.57 Impact Factor
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